Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the examination of imported malaria cases in Japan, the indirect fluorescent antibody test was confirmed as the most reliable serological technique in the diagnosis of individual malaria cases. Based on this finding, malaria serological assessment was carried out in endemic areas in Haiti, Indonesia, Sudan and in Brazil Amazon. The serological survey was useful in finding latent foci in a controlled area, for the assessment of past epidemics, in the differentiation of epidemiological features of moving populations, and also in the potential risk assessment in the Sudan Gezira. It should be stressed that the serological survey is not used simply for amplification of parasite survey. Epidemiological features which are not shown by parasite rate is revealed by means of serology studied at community level particularly after a successful malaria control operation. The newly developed malaria ABC-ELISA is a much simpler technique than the indirect fluorect fluorescent antibody test and will be useful in field surveys because the test can be made without electrical equipment. Through seroepidemiological studies the 47kD parasite molecule was noted. This parasite molecule was presented by the sera taken at the acute stage of infection. Detailed molecular and genetical studies are now being undertaken for the characterization of the high-lighted parasite substance.
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PMID:Malaria immuno--epidemiology--a trial to link field study with basic science. 205 56

An avidin biotin peroxidase complex enzyme-linked immunosorbent assay (ABC-ELISA) was examined for the diagnosis of malaria in a controlled area in Sudan Gezira. The titers of the ABC-ELISA coincided with those of the IFAT. The method was more sensitive than the ordinary ELISA as the final enzyme reaction was amplified through the use of the ABC system. This allowed the resulting color spots on the dried plate wells to be read clearly with the naked eye. This test can be carried out without using major electrical equipment.
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PMID:An ABC-ELISA for malaria serology in the field. 240 25

Ninety-seven Zairian schoolchildren were evaluated for cognitive ability, health status, and quality of home environment. Children successfully treated for serious types of chronic intestinal parasites demonstrated significant improvements in K-ABC Spatial Memory, supporting this task as one of the more sensitive measures to changes in general health and neurological integrity. These findings were not obtained for successful treatment of low-grade malaria infection. Children initially negative for intestinal parasites tended to come from more economically and socially favorable home environments. They also demonstrated more dramatic improvements in visual-spatial analysis tasks. The implication is that the home environment factors conducive to chronic infestation with intestinal parasites are markers for favorability of the developmental milieu affecting long-term intellectual development.
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PMID:Effects of treatment for intestinal parasites and malaria on the cognitive abilities of schoolchildren in Zaire, Africa. 850 Apr 52

Late stages of Plasmodium falciparum-infected erythrocytes (IRBCs) frequently sequester in the placentas of pregnant women, a phenomenon associated with low birth weight of the offspring. To investigate the physiological mechanism of this sequestration, we developed an in vitro assay for studying the cytoadherence of IRBCs to cultured term human trophoblasts. The capacity for binding to the syncytiotrophoblast varied greatly among P. falciparum isolates and was mediated by intercellular adhesion molecule 1 (ICAM-1), as binding was totally inhibited by 84H10, a monoclonal antibody specific for ICAM-1. Binding of the P. falciparum line RP5 to the syncytiotrophoblast involves chondroitin-4-sulfate (CSA), as this binding was dramatically impaired by addition of free CSA to the binding medium or by preincubation of the syncytiotrophoblast with chondroitinase ABC. ICAM-1 and CSA were visualized on the syncytiotrophoblast by immunofluorescence, while CD36, E-selectin, and vascular cell adhesion molecule 1 were not expressed even on tumor necrosis factor alpha (TNF-alpha)-stimulated syncytiotrophoblast tissue, and monoclonal antibodies against these cell adhesion molecules did not inhibit cytoadherence. ICAM-1 expression and cytoadherence of wild isolates was upregulated by TNF-alpha, a cytokine that can be secreted by the numerous mononuclear phagocytes present in malaria-infected placentas. These results suggest that cytoadherence may be involved in the placental sequestration and broaden the understanding of the physiopathology of the malaria-infected placenta.
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PMID:Cytoadherence of Plasmodium falciparum to intercellular adhesion molecule 1 and chondroitin-4-sulfate expressed by the syncytiotrophoblast in the human placenta. 911 59

Adherence of erythrocytes infected with mature asexual Plasmodium falciparum parasites (iRBC) to microvascular endothelial cells contributes to the pathology of P. falciparum malaria. It has been shown that the variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) confers adhesion to a wide range of cell surface receptors. Previously, the cysteine-rich interdomain region (CIDR) of PfEMP1 has been identified as binding site to CD36. We provide evidence that the same region can also mediate binding to chondroitin sulfate A (CSA). CIDR domains of two different parasite strains were expressed in Escherichia coli as a 6xHis-tagged protein. Purified recombinant protein bound to Chinese hamster ovary (CHO) cells which naturally express chondroitin sulfate A. Treatment of wild-type CHO cells with chondroitinase ABC reduced binding up to 94.4%. Competitive binding using soluble CSA inhibited binding to CHO cells by up to 100% at 2 mg/ml and by 62.4% at 0.5 mg/ml, whereas 1 mg/ml heparan sulfate had only a little effect (18.1%). In contrast, a recombinant 6xHis-tagged DBL1 domain showed no binding to wild-type CHO cells. Such an approach of analyzing various domains of PfEMP1 as recombinant proteins may elucidate their functions and may lead to novel anti-adherence therapeutics, especially for maternal malaria infections.
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PMID:Plasmodium falciparum: cloned and expressed CIDR domains of PfEMP1 bind to chondroitin sulfate A. 1091 Jul 12

Twenty-nine Senegalese children with a history of cerebral malaria (CM) performed more poorly on the Kaufman Assessment Battery for Children (K-ABC) Simultaneous Processing domain and on the Test of Variables of Attention (TOVA) attention capacity indicators in comparison with a matched control group. Thus, CM can disrupt neuropsychological integration during critical developmental periods, impacting on global neurological integrity, attentional vigilance, perceptual acuity, and subsequent development of visual-spatial processing and memory foundational to global cognitive ability. A subsequent structural equation model confirmed that rural children are at greater risk for CM, subsequent attention deficits, and other developmental risk factors in addition to the CM impact on K-ABC performance. We document CM as one of a host of developmental risk factors within the complex web of poverty in sub-Saharan Africa, which limit children's ability to achieve their full intellectual potential and, thus, extend the human cost of the disease beyond general measures of mortality and morbidity.
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PMID:Effects of early cerebral malaria on cognitive ability in Senegalese children. 1239 24

An important pathogenic complication of malaria during human pregnancy is sequestration of Plasmodium-infected red blood cells (iRBCs) in the placental intervillous spaces. This sequestration is thought to be mediated in part by binding of the iRBCs to receptors expressed on the syncytiotrophoblast (ST) membrane. We report here the use of a dynamic system to study the consequences of this cytoadherence on ST function using human syncytiotrophoblast and the choriocarcinoma cell line, BeWo. Laboratory isolates of Plasmodium falciparum were selected for their ability to bind to ST and used to investigate binding-induced cellular changes in the ST. Treatment of the ST cells with chondroitinase ABC suggested that the selected parasites bind predominantly to chondroitin sulfate A, but other receptors for parasite binding may be involved. Intracellular signaling in the ST induced by iRBCs binding was investigated by assessing tyrosine phosphorylation of ST proteins following iRBC binding. We demonstrate for the first time that iRBC cytoadherence to syncytiotrophoblast enhances tyrosine phosphorylation of a series of proteins in these cells. This approach will be useful in further studies of ST function in the malaria-infected placenta, the dynamics of selection of syncytiotrophoblast-binding parasites, and the identification of new receptors for parasite cytoadherence in the placenta.
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PMID:Plasmodium falciparum-infected red blood cells selected for binding to cultured syncytiotrophoblast bind to chondroitin sulfate A and induce tyrosine phosphorylation in the syncytiotrophoblast. 1600 22

Heavy metals are required by all organisms for normal function, but high levels of heavy metals are toxic. Therefore, homeostasis of these metals is crucial. In the human malaria-causing agent Plasmodium falciparum, the mechanisms of heavy metal transport have yet to be characterized. We have developed a P. falciparum line resistant to heavy metals from a wild-type line sensitive to heavy metals. A molecular and biochemical analysis of the involvement of the P. falciparum multidrug resistance 2 (pfmdr2) gene, an ABC-type transporter, in heavy metal homeostasis was studied. Using a novel uptake assay applied on these two strains, it was demonstrated that, when exposed to heavy metals, the sensitive line accumulates metal, whereas no accumulation was observed in the resistant line. The accumulation occurs within the parasite itself and not in the cytoplasm of the red blood cell. This difference in the accumulation pattern is not a result of amplification of the pfmdr2 gene or of a change in the expression pattern of the gene in the two lines. Sequencing of the gene from both lines revealed a major difference; a stop codon is found in the sensitive line upstream of the normal termination, resulting in a truncated protein that lacks 188 amino acids that contain a portion of the essential cytoplasmatic transporter domain, thereby rendering it inactive. In contrast, the resistant line harbors a full-length, active protein. These findings strongly suggest that the PFMDR2 protein acts as an efflux pump of heavy metals.
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PMID:pfmdr2 confers heavy metal resistance to Plasmodium falciparum. 1684 28

Drug resistance, an all too frequent characteristic of cancer, represents a serious barrier to successful treatment. Although many resistance mechanisms have been described, those that involve membrane-resident proteins belonging to the ABC (ATP binding cassette) transporter superfamily are of particular interest. In addition to cancer, the ABC transporter proteins are active in diseases such as malaria and leishmaniasis. A recent renaissance in lipid metabolism, specifically ceramide and sphingolipids, has fueled research and provided insight into the role of glycosphingolipids in multidrug resistance. This article reviews current knowledge on ceramide, glucosylceramide synthase and cerebrosides, and the relationship of these lipids to cellular response to anticancer agents.
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PMID:Glycosphingolipids and drug resistance. 1701 Mar 4

Transport ATPases can be lumped into four distinct types, P, F, V, and ABC, with the first three designated 20 years ago (Pedersen, P.L. and Carafoli, E., Trends Biochem. Sci. 12, 146-150, 1987) and the ABC type included more recently. The mini-reviews (>20) that comprise this volume of the Journal of Bioenergetics and Biomembranes describe work presented at the 2007 FASEB Conference (6th) on Transport ATPases (Kathleen Sweadner, Chair; Rajini Rao, Co-Chair). Since these conferences began in 1997, the "transport ATPase field" has seen tremendous progress. Advances include a much better understanding of the structure, mechanism, and regulation of each of the four major ATPase types as well as their physiological and medical relevance. In fact, the transport ATPase field has entered a new era in which work on these enzymes is likely to contribute to new therapies for multiple diseases that affect both people and animals. Among these are cancer and heart disease, mitochondrial diseases, osteoporosis, macromolecular degeneration, immune deficiency, cystic fibrosis, diabetes, ulcers, nephro-toxicity, hearing loss, skin disorders, lupus, and malaria. In addition, as several members of the transport ATPase family include those involved in drug resistance their study may help alleviate this recurring problem in drug development. Finally, the transport ATPase field is also paving the way for nanotechnology focused on nano-motors with work on the F-type ATPases (F(0)F(1)) leading the way. These ATPases driven in reverse by a proton gradient have the capacity to interconvert electrochemical energy into mechanical energy and finally into chemical energy conserved in the terminal bond of ATP. In mammalian mitochondria these events occur on a larger complex or "nano-machine" called the "ATP synthasome" that consists of the ATP synthase in complex formation with carriers for P(i) and ADP/ATP.
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PMID:Transport ATPases into the year 2008: a brief overview related to types, structures, functions and roles in health and disease. 1817 9


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